Original ContributionsColloid Solutions for Fluid Resuscitation in Patients with Sepsis: Systematic Review of Randomized Controlled Trials
Introduction
Sepsis is a systemic illness caused by a known or suspected microbial invasion of normally sterile parts of the body. It is a term that specifically serves to distinguish an illness of microbial origin from an identical clinical syndrome that can arise in several nonmicrobial conditions. Severe sepsis is accompanied by organ dysfunction or hypoperfusion or hypotension. Finally, when severe sepsis is accompanied by hypotension or need for vasopressors despite adequate fluid resuscitation, it turns into septic shock (1). Sepsis is considered as the leading cause of death in noncoronary intensive care units (ICUs) (2). In the United States, a large epidemiological study of up to 6 million people gave an incidence of 3 per 1000 population per year, or about 750,000 cases a year. Mortality was 28.6% or 215,000 deaths nationally. The average cost per case was $22,100, with annual total costs of $16.7 billion nationally. The incidence of sepsis and the number of sepsis-related deaths is increasing 3, 4, 5.
Fluid resuscitation has been shown to improve survival for patients presenting with septic shock in a randomized, controlled, single-center study (6). Microcirculatory dysfunction is a pivotal element of the pathogenesis of severe sepsis and septic shock (7). Misdistribution of fluid in the microcirculation is typical of septic shock that is caused by endotoxin-induced endothelial damage (8). Colloids contain particles that are large enough to gain an oncotic pressure across the microvascular membrane. Compared with crystalloids, they have greater intravascular persistence. They are able to correct volume loss rapidly, improve blood flow, and have a long duration of their effect (9). The pharmacological and pharmacodynamic properties of the various colloids differ widely (10). International guidelines suggest infusion of either natural or artificial colloids or crystalloids (11). No evidence supported the effectiveness of one type of fluid solution over another (12). However, as the volume of distribution is much larger for crystalloids than for colloids, resuscitation with crystalloids alone requires more fluid and results in more edema, and might be inferior to combination therapy with colloids (11). Colloid solutions combined with crystalloids are widely used for replacement of fluid volume, particularly in Europe (9).
These solutions can be natural colloid (e.g., human albumin, plasma protein fraction) or synthetic colloid (e.g., dextrans, hydroxyethyl starch solution [HES], and gelatin) (13). However, it is still uncertain which colloid is the best in sepsis. The duration of intravascular persistence of colloids depends on molecular size, shape, ionic charge, and the porosity of the capillary endothelium (10). Albumin is the colloid containing particles of consistent molecular weight (monodisperse). The other colloids are polymers and contain particles with a wide range of molecular weights (14). This can make colloids vary in their safety and effectiveness. Compared with other colloidal solutions, human albumin solutions are expensive and limited in availability. Dextrans seems to have the most unfavorable risk-to-benefit ratio among the currently available synthetic colloids due to their relevant anaphylactoid potentialities, risk of renal failure, and, particularly, their major impact on hemostasis. The effects of gelatin on kidney function are currently unclear, but potential disadvantages of gelatin include high anaphylactoid potentialities and a limited volume effect compared with dextrans and HES (15). Modern HES preparations have the lowest risk of anaphylactic reactions among the synthetic colloids. Older HES preparations have repeatedly been reported to impair renal function and hemostasis 16, 17. There have been previous systematic reviews suggesting that no one colloid solution is more effective or safer than any other colloids for fluid resuscitation in patients who need volume replacement (13). Sepsis is one of the diseases associated with hypovolemia or hypoperfusion, which is different from other diseases (such as bleeding and capillary leakage) on pathophysiological mechanism. Consequently, to quantify the effect on mortality and the safety of different colloids in the management of critically ill patients with sepsis, we conducted this systematic review to identify and synthesize all available evidence.
Section snippets
Objectives
Our aim was to assess the effects on mortality and safety of different colloid solutions in patients with sepsis requiring volume replacement by examining direct comparisons of colloid solutions.
Types of studies
Randomized controlled trials were chosen because they are the best method for revealing the effects of a therapeutic intervention. Because quasi-randomized controlled trials used a method of allocating participants to different forms of care that is not truly random, they were excluded. Because the
Study Selection
A total of 436 possible relevant studies were identified; 75 were selected and the full copies were obtained. Twenty-three studies were selected and more detailed methodological evaluation done. Only 17 studies were finally identified as meeting the inclusion criteria (Figure 1). Two trials were excluded because the data did not meet the outcome measures; letters for the related trial data were sent to the investigators, but no response was received. Two trials were excluded because they were
Discussion
Development of synthetic colloids was markedly driven during times of war to facilitate transport of wounded soldiers to where blood transfusions were available. Synthetic colloids are popular in Europe and HES has become one of the most frequently used colloidal plasma expanders worldwide (42). Previous systematic reviews have assessed the effects on mortality of different colloid solutions in critically ill and surgical patients requiring volume replacement (13). However, there was wide
Conclusions
This review did not identify sufficient evidence to prove one colloid solution is more effective and safer than another for treating patients with sepsis. The severity score is improved in HES, but the confidence intervals are wide. As the report was based on relatively small trials in which there were only a small number of deaths, the results must be considered with caution. Additional randomized controlled trials that are conducted rigorously and with mortality as the end point are needed to
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